Serosal cavity metastases of malignant tumor seriously affects the quality of life and survival time of patients with cancers in advanced stage. VEGFR1 is frequently expressed in breast cancer, ovarian cancer, lung cancer, gastric cancer and other malignant tumors and their metastases. The VEGFR1/PD-L1 dual-targeting CAR-T will be investigated in cancer patients with serosal cavity metastases.
In this study, VEGFR1 will be used as the general target of serosal cavity metastasis of malignant tumor, and the dual-targeting CAR-T of VEGFR1/PD-L1 will be injected in to pleural or peritoneal cavity of patients with advanced serous cavity metastases, such as ovarian cancer, breast cancer, lung cancer and gastric cancer, who had nearly no response to standard treatment. The safety and effectiveness will be evaluated. The safety evaluation standard refers to the standard of CTCAE 5.0. The evaluation standard of effectiveness refers to the evaluation standard of solid tumor curative effect RECIST 1.1 to evaluate the curative effect. There are two part of this study, the first is dose escalation part, 18 patients with malignant tumor (failure of standard treatment will be enrolled at least, patients with peritonea cavity metastases are planned to be enrolled in the cohort 1, and those with pleural cavity metastasis are enrolled in the cohort 2. The second is dose expansion part, the curative effect has observed in the first part, and after the DLT observation period of the related dose group was finished, the PI will decided whether to conduct the dose expansion research finally. It was planned to enroll 40 patients with serous cavity metastases , two cohorts were divided the same as mentioned above in dose escalation part.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
58
In the dose escalation part, the dose levels will be escalated following a traditional escalation scheme for 3+3 design. In the dose expansion part, patients will be assigned to different groups based on pleural or peritoneal metastases condition.
West China Hospital, Sichuan University
Chengdu, Sichuan, China
RECRUITINGAEs will be recorded and evaluated by CTCAT 5.0.
Safety
Time frame: 28 days
Recommended phase II dose (RP2D).
Efficacy dose
Time frame: Approximately 18 months.
Therapeutic efficacy will be evaluated according to RECIST1.1.
Ant-tumor effects
Time frame: Approximately 18 months.
Dose-limiting toxicity (DLT) will be assessed by CTCAE 5.0.
Tolerability evaluation
Time frame: 28 days
Objective Remission Rate (ORR).
Include CR (complete response) and PR (partial response).
Time frame: 3 months
Progression-Free Survival (PFS ).
The time from CAR-T administration to disease progression or death.
Time frame: Approximately 18 months.
Duration Of Control Rate (DCR).
The number of cases in which response (PR + CR) and stable disease (SD) are achieved from the start of cell infusion/the total number of evaluable cases (%).
Time frame: 3 months
Duration Of Response (DOR).
It refers to the time from the first evaluation of CR or PR to the first evaluation of PD(Progressive Disease) or death from any reason.
Time frame: Approximately 18 months.
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Overall-Survival (OS).
It defined as the time from randomization to death from any cause, is a direct measure of clinical benefit to a patient. Patients alive or lost to follow-up are censored.
Time frame: Approximately 18 months.
Anti-CAR antibody production
Immunogenicity
Time frame: 12 months.
CAR-T cell numbers.
PK/PD
Time frame: 12 months.